Announcement of Requirements and Registration for the National Center for Advancing Translational Sciences ASPIRE Design Challenge 4: Biological Assays for Translational Innovation in Pain, Opioid Use Disorder and Overdose

Summary of NCATS ASPIRE Design Challenges

The National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH), is inviting novel design solutions for A Specialized Platform for Innovative Research Exploration (NCATS ASPIRE) Design Challenges as part of the NCATS ASPIRE Program. The goal of the NCATS ASPIRE Design Challenges is to reward and spur innovative and catalytic approaches toward solving the opioid crisis through development of (1) novel chemistries, (2) data mining and analysis tools and technologies, and (3) biological assays that will revolutionize discovery, development and pre-clinical testing of next-generation, safer and non-addictive analgesics to treat pain, as well as new treatments for opioid use disorder (OUD) and overdose. The first phase of these prize competitions is implemented through a suite of concurrent companion Design Challenges that comprises separate Challenges for each of four areas — chemistry database, electronic laboratory knowledge portal for synthetic chemistry, algorithms and biological assays — and an additional Challenge for a combined solution to at least two Challenge areas. At this stage, innovators are expected to submit designs, not final products or prototypes.

NCATS envisions following these Design Challenges with a follow-on but distinct final Reduction-to-Practice Challenge, which will aim to invoke further scientific and technological development of the model system. Winners of the Design Challenges will be invited to present their designs so that, in the envisioned follow-up Reduction-to-Practice Challenge, an open competition, teams will be able to form multidisciplinary collaborations to advance and integrate the most feasible and promising approaches to the multiple Challenges into a single integrative platform. Innovators will be invited to demonstrate final solutions.

The NCATS ASPIRE Design Challenges are part of NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative will bolster research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative.

NCATS refers to participants in the NCATS ASPIRE Design Challenges as “innovators,” because all solutions will require highly innovative approaches to achieve success. Innovators should clearly state how and why the proposed solution would provide significant advances over currently available tools. Innovators may choose to compete in one or more individual Challenges to address a single area (Challenges 1-4) or propose a combined solution for at least two Challenge areas (Challenge 5).

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Summary of NCATS ASPIRE Design Challenge 4: Biological Assays for Translational Innovation in Pain, Opioid Use Disorder and Overdose

Biological assays

Challenge 4 aims to address the need for novel, physiologically relevant biological assays that can accurately replicate the safety profile and effectiveness of existing drugs to treat addiction and/or overdose and that can be reliably used in predictive assessments of new analgesics or drugs to treat addiction and/or overdose and/or be able to anticipate the degree of addictiveness of an analgesic prior to clinical testing. This Challenge requires submission of only a detailed description of the design of the assay(s), not the final working assay(s).

Evaluation criteria that reviewers will be asked to address are specified below.

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Dates and Deadlines

Solutions must be submitted to Challenge.gov by NOON Eastern Time on May 31, 2019. 

The Challenge begins: December 31, 2018 
Submission period: December 31, 2018-May 31, 2019
Judging period: June 17, 2019-August 2, 2019
Winners announced: August 2019

For further information send an email to NCATSASPIREChallenge@mail.nih.gov.

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The IC’s Statutory Authority to Conduct the Challenge

The general purpose of NCATS is to coordinate and develop resources that leverage basic research in support of translational science and to develop partnerships and work cooperatively to foster synergy in ways that do not create duplication, redundancy and competition with industry activities (42 USC 287(a)). In order to fulfill its mission, NCATS supports projects that will transform the translational process so that new treatments and cures for diseases can be delivered to patients faster by understanding the translational process in order to create a basis for more science-driven, predictive and effective intervention development for the prevention and treatment of all diseases. NCATS is also conducting this Challenge under the America Creating Opportunities to Meaningfully Promote Excellence in Technology, Education, and Science (COMPETES) Reauthorization Act of 2010, 15 U.S.C. 3719. In line with these authorities, this Challenge(s) will lead to innovative designs for developing technology to revolutionize discovery, development and pre-clinical testing of new and safer treatments of pain, opioid use disorder (OUD), and overdose; the result will be generalizable tools that will be widely available to fill longstanding gaps that have impeded the marriage of basic and translational sciences.

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Subject of the Challenge Competition

Challenge 4. Biological Assays for Translational Innovation in Pain, Opioid Use Disorder and Overdose. This Challenge aims to reward and spur innovative solutions to the development of a novel physiologically relevant biological assay to advance pre-clinical discovery and development of non-addictive treatments for pain, drug addiction or overdoses. This Challenge requires submission of only a detailed description of the design of the assay(s), not the final working assay(s). Current in vitro assays and in vivo models to study pain and addiction and test potential treatments are very limited. Pharmacological probe, lead and drug development have traditionally utilized canonical cell lines (such as CHO or HEK293) that heterologously express the molecular target of interest, and studies that are performed in animal models often do not fully recapitulate human physiology and may identify candidate compounds without effects in more human physiology-relevant systems. Therefore, NCATS is inviting innovators to propose and develop novel “disease-in-a-dish” assays of pain perception, addiction or overdose that advance the understanding of different types of pain, identify differences in inter- and intra-individual pain and the associated risk of developing chronic pain and/or addiction and make possible the development of improved, non-addictive drugs to treat these conditions. 2D and 3D human disease-relevant screening platforms may include but are not limited to normal and diseased human iPSC-derived sensory/pain neurons (such as peripheral, dorsal root ganglia [DRG], spinal cord and thalamus); neurons relevant to reward pathways; and other tissues important for pain, addiction and overdose, including blood-brain barrier (BBB). The assays will be adjudicated on their physiological relevance, robustness and reproducibility, and their future potential to be amended to automation and scalability for medium to high-throughput screening assays. Initially, the assay can be designed for low-throughput screening; it is expected that even at low throughput, multiple technical replicates will be compared in the same experiment. Eventually, the assay should be amenable to automation and scalable to medium- (96-well plate) to high-throughput screening (using, for example, high-content imaging, drug validation/toxicity, functional genomic screening).

The innovators are encouraged to consult NCATS’ Assay Guidance Manual to learn more about appropriate designing of a drug screening assay.

For the envisioned Reduction-to-Practice phase, the innovators will be expected to demonstrate the viability rate of cells in 2D or 3D models, at a particular throughput (90% viable), and provide data indicating how the functional morphological features are maintained in the system over time.

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Concurrent Companion NCATS ASPIRE Design Challenges

NCATS has recently explored the development of A Specialized Platform for Innovative Research Exploration (ASPIRE) to aid in the discovery and development of novel and effective treatments while at the same time making the process faster and more cost-effective. The NCATS ASPIRE Program aims to develop and integrate automated synthetic chemistry, biological screening and artificial intelligence approaches in order to significantly advance our understanding of the relationship between chemical and biological space and enable further access into biologically relevant chemical space. The platform will utilize currently available knowledge to develop innovative algorithms and predict and synthetize novel structures capable of interacting with specific targets; enable small-scale synthesis of the predicted molecules; and incorporate in-line, rapid biological testing of the molecules. Any new data obtained through this process would then be fed back into the system to further improve design, synthesis and biological characteristics of molecules.

Over 25 million people in the United States experience pain every day (2012 National Health Interview Survey data) and need safe, addiction-free treatments to alleviate their suffering. This clinical demand is of tremendous importance given that overprescribing of opioids for managing acute and chronic pain has fueled the current epidemic of opioid use disorder and overdose deaths, and the effectiveness of opioids for long-term pain management is being questioned. Safe, effective and non-addictive drugs (small molecules and biologics) to treat pain, mitigate addiction and reverse overdose are key to addressing the opioid crisis. Given failures and limitations of previous drug development efforts, drugs that recognize novel targets, have novel structures and can be identified in human-based, physiologically relevant in vitro systems are needed. To advance the NCATS ASPIRE Program and reward and spur innovative solutions to the development of new drugs for pain, addiction and overdose, NCATS is issuing this Challenge and concurrent companion Challenges to highly collaborative innovators interested in designing novel approaches that would lead to efficacious and non-addictive pain treatments and/or novel treatments for addiction and overdose.

The ultimate goal of the NCATS ASPIRE Program is development of a platform that a wide spectrum of scientists can use to advance their translational science relevant to development and pre-clinical testing of new and safer treatments of pain, opioid use disorder (OUD) and overdose. Furthermore, it is essential that the approaches described and proposed here are applicable to any translational problem.

Challenge 1: Integrated Chemistry Database for Translational Innovation in Pain, Opioid Use Disorder and Overdose rewards and spurs innovative solutions to the design of an open-source, controlled-access database that incorporates all currently available chemical, biological and clinical data of known opioid- and non-opioid-based analgesics, drugs of abuse and drugs used to treat drug abuse.

Challenge 2: Electronic Synthetic Chemistry Portal for Translational Innovation in Pain, Opioid Use Disorder and Overdose rewards and spurs innovative solutions to the design of a next-generation open-source electronic lab notebook (eLN) that collects, organizes and analyzes data relevant to the chemical synthesis and analyses of known opioid- and non-opioid-based analgesics, drugs of abuse and molecules used to treat drug abuse into an electronic laboratory knowledge portal for synthetic chemistry (electronic synthetic chemistry portal; eSCP).

Challenge 3: Predictive Algorithms for Translational Innovation in Pain, Opioid Use Disorder and Overdose rewards and spurs innovative solutions to the design of open source, advanced machine learning algorithms that would facilitate the discovery of novel, efficacious and non-addictive analgesics and/or treatments for drug abuse by utilizing the data collected in open source databases (Challenge area 1), eSCPs (Challenge area 2) and biological assays (Challenge area 4).

Challenge 5: Integrated Solution for Translational Innovation in Pain, Opioid Use Disorder and Overdose rewards and spurs the design of innovative, comprehensive solutions to the opioid crisis through innovative approaches that integrate solutions to at least two Challenge areas (Challenges 1-4: Integrated Chemistry Database, Electronic Synthetic Chemistry Portal, Predictive Algorithms and Biological Assays, respectively) into a single platform.

Note: Each component of Challenge 5 (above) is also available as an individual Challenge at Challenge.gov.

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Registration Process for Innovators

Innovators may access the registration and submission platform in one of the following ways:

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The Prize

Amount of the Prize; Award-Approving Official. 

The total prize purse is $500,000. Up to five (5) winners will be selected. NIH reserves the right to cancel, suspend and/or modify this Challenge at any time through amendment to this notice. In addition, NIH reserves the right to not award any prizes if no solutions are deemed worthy. The Award Approving Official will be Christopher P. Austin, M.D., Director of the National Center for Advancing Translational Sciences (NCATS).

Payment of the Prize. Prizes awarded under this competition will be paid by electronic funds transfer and may be subject to federal income taxes. HHS/NIH will comply with the Internal Revenue Service withholding and reporting requirements, where applicable.

Matching Requirement. A for-profit private entity solver (innovator) receiving a prize under this Challenge must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018. Such a winner(s) will be required to demonstrate that matching funds and/or in-kind contributions were committed to achieve the winning solution. Such a winner(s) must identify the source and amount of funds used to meet the matching requirement or describe how the value for in-kind contributions was determined.

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Evaluation and Winner Selection

Basis upon Which Winners Will Be Selected. A panel of federal and non-federal reviewers, with expertise directly relevant to the Challenge, will evaluate the solutions based on feasibility and ability to achieve the criteria listed below. The solutions and evaluation statements from the technical panel will then be reviewed by federal employees serving as judges, who will select the Challenge winners, subject to the final decision by the Award Approving Official. The NCATS will provide feedback from the technical experts and judges to the winners and non-winners on their respective submissions.

The points assigned to each set of evaluation criteria are guidelines from NCATS to suggest which scientific milestones are of emphasis and interest to the Center. All winners are highly encouraged to participate in future NCATS ASPIRE Reduction-to-Practice Challenges that NCATS is planning. 

Only complete submissions will be reviewed.

Submission Requirements and Template

Instructions for submission: Please format the proposal using the Submission Template and submit it to Challenge.gov as a PDF. Brief instructions on the submission process can be found below. Detailed instructions are provided in the submission template.

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Basis upon Which Submissions Will Be Evaluated

Challenge 4. Biological Assays for Translational Innovation in Pain, Opioid Use Disorder and Overdose. This Challenge aims to address the need for novel, physiologically relevant biological assays that accurately replicate the safety profile and effectiveness of existing drugs and that can be reliably used in predictive risk assessments of new analgesics or drugs to treat addiction and/or overdose to molecular signature(s) and/or be able to anticipate the degree of addictiveness of an analgesic prior to clinical testing. This Challenge requires submission of only a detailed description of the design of the assay(s), not the final working assay(s).

The goal of this Challenge is to reward and spur innovative solutions to the development of a novel physiologically relevant biological assay to advance pre-clinical discovery and development of non-addictive treatments for pain, drug addiction or overdoses. Current in vitro assays and in vivo models to study pain and addiction and test potential treatments are very limited. Pharmacological probe, lead and drug development have traditionally utilized canonical cell lines (such as CHO or HEK293) that heterologously express the molecular target of interest, and studies that are performed in animal models often do not fully recapitulate human physiology and may identify candidate compounds without effects in more human physiology-relevant systems. Therefore, NCATS is inviting innovators to propose and develop novel “disease-in-a-dish” assays of pain perception, addiction or overdose that advance the understanding of different types of pain, identify differences in inter- and intra-individual pain and the associated risk of developing chronic pain and/or addiction and make possible the development of improved, non-addictive drugs to treat these conditions. 2D and 3D human disease-relevant screening platforms may include but are not limited to normal and diseased human iPSC-derived sensory/pain neurons (such as peripheral, dorsal root ganglia [DRG], spinal cord, thalamus); neurons relevant to reward pathways; and other tissues important for pain, addiction and overdose, including blood-brain barrier (BBB). The assays will be adjudicated on their physiological relevance, robustness and reproducibility, and their future potential to be amended to automation and scalability for medium to high-throughput screening assays.

Initially, the assay can be designed for low-throughput screening; it is expected that even at low throughput, multiple technical replicates will be compared in the same experiment. Eventually, the assay should be amenable to automation and scalable to medium- (96-well plate) to high-throughput screening (using, for example, high-content imaging, drug validation/toxicity, functional genomic screening).

The innovators are encouraged to consult NCATS’ Assay Guidance Manual to learn more about appropriate designing of a drug screening assay.

For the envisioned Reduction-to-Practice phase, the innovators will be expected to demonstrate the viability rate of cells in 2D or 3D models, at a particular throughput (90% viable), and provide data indicating how the functional morphological features are maintained in the system over time.

Judging criteria:

Evaluation Criterion 1: Impact and Innovation (20 points)

  • To what degree is the proposed assay creative, original and biologically relevant?
  • To what extent is the assay design feasible? Does it have a high likelihood of success?
  • To what extent is the proposed solution innovative, and how high is its potential to significantly improve the state of science?
  • To what extent will the proposed assay accelerate discovery, development and pre-clinical testing of new and safer treatments of pain and/or opioid use disorder (OUD) and overdose?
  • To what extent are novel concepts, approaches, methodologies and technologies proposed or existing approaches applied to the design in a novel way?
  • To what extent does the proposed assay incorporate cross-disciplinary techniques (e.g., cell biology, imaging, electronics, engineering, etc.)?
  • Is the proof-of-concept data using currently available pain drugs, drugs of addiction and/or addiction/overdose treatments proposed?
  • How well will the assay(s) demonstrate biological and physiological relevance to a specific application (pain, addiction or OUD)?
  • Is a relevant proof-of-concept study of the innovators’ choice proposed for the subsequent Reduction-to-Practice stage?

Evaluation Criterion 2: Model System and Assay Design (20 points)

  • How physiologically relevant is the proposed model system that is being assayed?
  • To what extent is the assay designed and amenable for validation taking into consideration the target being studied using appropriate drugs/compounds and controls?
  • Are the appropriate cell types co-cultured in the model system at physiological ratios? What is the origin of the cells, and how relevant are the cell types to the model system?
  • What is the assay’s readout (e.g., biochemical, fluorometric, phenotypic), and is this sufficient to maximize the value of the assay?
  • How long will it take to perform the assay in full? Is the timing of the assay appropriate? (What is an assay’s development cycle time?)
  • How many technical replicates will the assay support?
  • Can the assay be multiplexed?
  • Are secondary/specificity/selectivity assays proposed to confirm the initial data?
  • What are instrumental, computational and data storage requirements?

Evaluation Criterion 3: Assay Robustness, Reproducibility and Scalability (10 points)

  • How well does the proposal describe plans to assess inter- and intra-laboratory utility, transferability and reproducibility?
  • How well are the protocols described? Are the protocols sufficiently clear and detailed to facilitate inter- and intra-laboratory utility and reproducibility?
  • For the Reduction-to-Practice phase, how would an assay’s robustness and reproducibility be demonstrated?
  • Is the assay designed to minimize bias — for example, are the cells seeded, differentiated, cultured manually?
  • Are appropriate experiments proposed that will address the stability of the assay components and reagents?
  • To what extent is the data collection and analysis automated?
  • To what degree could the assay be integrated with other Challenge(s) in a subsequent Reduction-to-Practice phase?

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